The long-term objective of this proposal is to establish the number and types of genetic control mechanisms that are utilized by mammals in regulating the activity of specific enzymes and entire pathways. The specific aims of this project are: (1) to further elucidate the mechanism whereby the Lv locus in mice controls the rate of synthesis of sigma-aminolevulinate dehydratase (ALD); (2) to study the apparent lack of control of the Lv locus on ALD in spontaneous and transplantable hepatomas; (3) to determine the effect of specific deleterious recessive mutations such as obese (ob), and diabetes (db) on the spontaneous tumor incidence in susceptible strains of mice; and (4) to study other interesting biochemical mutants that are applicable to our continuing search for new gene systems controlling metabolic pathways.